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PubMed1996

Serum immunoreactive bone sialoprotein as a new marker of bone turnover in metabolic and malignant bone disease.

Bone sialoprotein (BSP) is a phosphorylated glycoprotein with a M(r) of 70-80 kDa that accounts for approximately 5-10% of the noncollagenous proteins of bone. Due to its relatively restricted distribution to mineralized tissues, BSP may serve as a potential marker of bone metabolism. Employing a recently developed RIA, serum BSP was measured in 133 healthy subjects, aged 20-80 yr, and in patients with primary hyperparathyroidism (pHPT; n = 26), Paget's disease of bone (PD; n = 14), untreated multiple myeloma (MM; n = 32), and breast cancer with bone metastases (BC; n = 19). Results were compared to clinical and laboratory data, including serum total alkaline phosphatase as a marker of bone formation, and the urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption. In healthy adults, serum BSP values ranged between 5.0-21.6 ng/mL (5-95% interval), with a median of 10.5 ng/mL (total group). In healthy females, a linear correlation was found between serum BSP and age (r = 0.51; P < 0.001), with significantly higher values in postmenopausal than in premenopausal women (13.3 +/- 4.8 vs. 9.0 +/- 3.8; P < 0.01). In the healthy group, BSP values did not change with body mass index, lumbar bone mineral density, serum calcium, serum creatinine, or serum total alkaline phosphatase levels. In contrast, a weak, but significant, correlation was observed between serum BSP and the urinary excretion of PYD and DPD. Compared to those in healthy controls, serum BSP levels were significantly higher in patients with pHPT, PD, MM, or BC (P < 0.01 for all groups). These differences remained after analyses were adjusted for age and sex. In pHPT, serum BSP levels were closely correlated to urinary PYD and DPD (r = 0.87 and 0.83, respectively; P < 0.01), whereas in PD, no correlation was observed between any of the bone markers. Serum BSP levels were highest in patients with MM, and there was a significant difference between early and advanced stages of the disease (30.2 +/- 8.0 vs. 64.3 +/- 6.8; P < 0.01). In a subgroup of 15 patients with metastatic BC, iv bisphosphonate treatment resulted in a rapid reduction of serum BSP levels to 40% of the baseline values within 4 days of treatment. In conclusion, BSP appears to be a sensitive marker of bone turnover, and the present data suggest that its serum levels predominantly reflect processes related to bone resorption.

Adult↗
PubMed1996

[Archiving of pathologic-anatomic findings in bone diseases and bone neoplasms in individual databanks. Experiences of a new enterprise with applicable outcome].

In this paper my experience with a databank for cases with bone diseases is reported. All cases which had been diagnosed in the newly formed Department of Bone Pathology of the University of Hamburg since 1970 were registered in uniform fashion. Adapting the system to state-of-the-art network structures required a lot of personal and financial investment. This could not be accomplished by university resources alone, but only in cooperation with other research funds. Now 76,000 cases can be routinely accessed and scientifically analysed.

Bone Diseases↗
PubMed1975

Serum immunoreactive parathyroid hormone and 25-hydroxyvitamin D in patients with uremic bone diseases.

Bone histologic parameters and serum iPTH and 25-OHD were measured in 20 patients with end-stage renal failure treated with hemodialysis. By bone histologic criteria, the patients were divided into three groups: mild, osteomalacic, and fibrotic. The increase in serum iPTH was much greater in the fibrotic group than in the mild or osteomalacic groups. In the uremic patients as a group, there were significant correlations between serum iPTH and both percent marrow fibrosis and percent resorbing surface. In the mild and fibrotic groups together, serum iPTH was also correlated with percent forming surface. This and other findings suggested that most of the bone changes in the mild and fibrotic groups could be explained by excess PTH. The difference in bone changes and in serum iPTH between the mild and fibrotic groups could be related to our eariler findings that duration of renal disease was much greater in the fibrotic than in the mild group. The lowest increment in serum iPTH was found in the osteomalacic group. In this group, percent resorbing surface was not increased and there was only a slight increase in marrow fibrosis. Thus in all three groups, serum iPTH appeared to reflect parathyroid status. The cause of the elevated serum iPTH and for the intergroup differences was not apparent inasmuch as serum calcium was normal in all three groups. Serum 25-OHD was significantly elevated in the osteomalacic and fibrotic groups. Because none of our patients had received preparations containing vitamin D, the elevated serum 25-OHD in the osteomalacic and fibrotic groups is consistent with altered vitamin D metabolism in these two groups. There was a direct relationship between percent osteroid area and serum 25-OHD. However, whether or not altered vitamin D metabolism contributed to the mineralization defect in uremic bone disease could not be established.

Adult↗
PubMed1994

Metabolic acidosis and bone disease.

Bone is the largest repository base in the body. Prolonged acid retention requires continuous buffering of acid if the organism is to survive. This paper discusses the role of bone buffering under both normal and altered conditions of acid-base homeostasis. We place particular emphasis on the roles of PTH and vitamin D in this process. We also discuss bone abnormalities in renal tubular acidosis and chronic renal failure.

Acidosis↗
PubMed1983

The influence of systemic bone disease on bone resorption following mandibular augmentation.

Reports of mandibular osseous augmentation that include individual results consistently reveal a wide range in resorption rates. The alveolar ridges may be sensitive indicators of changes in bone metabolism. Fourteen candidates for mandibular augmentation were examined for systemic bone disease (SBD) by history, serum biochemical analyses, and photon absorption densitometry of the radial midshaft. Four patients had decreased densitometry values. Transileal bone biopsies performed on these four all revealed SBD. In thirteen of the fourteen patients augmentation was performed by one of the five techniques described. One patient with SBD was not treated. Postoperative resorption results are not statistically significant, but the following clinical observations can be made: Two patients (Cases 3 and 10) with SBD that was not arrested had excessive resorption. One patient (Case 5) who had SBD successfully arrested preoperatively showed less than average resorption. One patient (Case 4) had no SBD but had great resorption. Therefore, unarrested SBD may contribute to increased postoperative resorption, but other unknown factors also contribute to excessive postoperative resorption.

Adult↗
PubMed2003

The lesson of temporary brittle bone disease: all bones are not created equal.

Temporary brittle bone disease (TBBD) is a recently described phenotype of multiple, unexplained fractures in the first year of life and predominantly in the first 6 months of life. There is usually no other injury such as bruising, subdural hematomas, retinal hemorrhages, or other internal organ injury. The susceptibility to fracture is transient, and there are no other radiographic or biochemical abnormalities noted in the standard evaluation that might suggest an underlying cause. The child abuse and pediatric radiology communities have, for the most part, been unwilling to accept this as a real condition, for they believe it is a ruse for child abuse. This review describes the experience of the author in evaluating infants with multiple unexplained fractures and the hypothesis that has emerged for explaining TBBD. The hypothesis is a prenatal application of the mechanostat/bone loading theory of bone formation and states that TBBD is caused by fetal immobilization which leads to fetal bone unloading and transient, relative osteopenia. Such susceptible infants can fracture with routine handling and present with a pattern of fractures that is similar to that which has been thought to be highly specific for child abuse. The review presents: (a) the evidence that indicates that normal fetal movement is important for normal fetal bone strength, (b) a critique of the radiologic approach in the diagnosis of child abuse in infants with multiple unexplained fractures, (c) observations that would indicate that child abuse is unlikely in infants with TBBD, and (d) new approaches to the infant with multiple unexplained fractures that would assist in accurate diagnosis.

Animals↗
PubMed2006

[Regulation of osteoclast activity: a new approach in the therapy of bone diseases].

Bone remodelling is process of constant resorption and formation of a bone. Osteoclasts are the cells responsible for bone resorption. Deregulation of osteoclast differentiation, activity or function can cause severe diseases, such as osteoporosis, osteopetrosis or rheumatoid arthritis. Advances in molecular biology of osteoclasts and osteoimmunology open new approaches for the specific and efficient therapy.

Animals↗
PubMed2005

The "functional muscle-bone unit": a two-step diagnostic algorithm in pediatric bone disease.

Bone densitometric data often are difficult to interpret in children and adolescents because of large inter- and intraindividual variations in bone size. Here we propose a functional approach to bone densitometry that addresses two questions. Is bone strength normally adapted to the largest physiological loads, i.e., muscle force? Is muscle force adequate for body size? Previously published reference data were used to evaluate results from children with preterminal chronic renal failure (n=11) and renal transplant recipients (n=15). In both groups mean height, muscle cross sectional area (MCSA), and bone mineral content (BMC) were low for age, but muscle MCSA was normal for height. In the renal transplant recipients the BMC/muscle MCSA ratio was decreased (P <0.05), suggesting that bone cortical strength was not adapted adequately to muscle force. In contrast, chronic renal failure patients had a normal cortical BMC/muscle MCSA ratio, suggesting that their musculoskeletal system was adapted normally to their (decreased) body size.

Adolescent↗
PubMedDate not supplied

Disappearance of 99mTc-MDP accumulation in metastatic bone disease during bone scintigraphy.

We describe a patient with progressive metastatic bone disease involving a pedicle of the lumbar spine, in whom serial bone scans were performed. Initially, increased radiotracer accumulation was evident, corresponding to an osteoblastic lesion found on CT. Later, radiotracer uptake appeared to be normal, while an expansile tumor causing osteolytic change was noted on CT. We suggest that false-negative bone scan can occur in the natural process of progressive bone metastasis.

Aged↗
PubMed1999

Metabolic bone disease in adults with inflammatory bowel disease.

Bone loss is seen frequently in those with inflammatory bowel disease (IBD). It appears to be more common in those with Crohn's disease than in those with ulcerative colitis. Corticosteroids play an important role in the development of osteoporosis. The prevalence of osteoporosis in IBD, the effects of corticosteroids on bone metabolism, and treatment options are reviewed.

Adult↗
PubMed1995

Clinical utility of a wheat-germ precipitation assay for determination of bone alkaline phosphatase concentrations in patients with different metabolic bone diseases.

Bone alkaline phosphatase was evaluated by wheat-germ lectin precipitation in several clinical conditions. The study included 33 premenopausal healthy women, 46 postmenopausal apparently healthy women, 19 growing children, 24 patients with Paget's disease, 31 patients with primary hyperparathyroidism and 66 patients with hepatobiliary diseases. In postmenopausal women the mean T score (i.e.: the number of SD below or above the mean for premenopausal women) was 2.6 +/- 1.3 (SD) for bone alkaline phosphatase and 1.61 +/- 1.21 for total alkaline phosphatase (p < 0.001). The T score for bone alkaline phosphatase provided a better discrimination from normals for both Paget's disease (22.1 +/- 27.8 versus 12.8 +/- 16 p < 0.001) and primary hyperparathyroidism (8.2 +/- 4.3 versus 4.6 +/- 3.7 p < 0.005 for bone alkaline phosphatase and total alkaline phosphatase respectively). After treatment with intravenous bisphosphonate the percent decrease of bone alkaline phosphatase was larger than that of total alkaline phosphatase both in patients with Paget's disease (-46% versus -72% p < 0.01) and in patients with primary hyperparathyroidism (-21% versus -47% p < 0.02) and an estimate of the precision (delta mean/SD of the delta mean) for bone alkaline phosphatase was 1.9-3.7 times higher than that of total alkaline phosphatase. In twelve osteoporotic patients treated for six months with oral alendronate the decrease in bone turnover was detected with significantly higher precision with bone alkaline phosphatase than with total alkaline phosphatase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

In vitro and in vivo antiresorptive effects of bisphosphonates in metastatic bone disease.

Bone metastases commonly occur in the course of malignant tumor disease. For many years, attempts have been made to identify factors for the management of cancer-induced skeletal complications. Nowadays, synthetic antiresorptive agents are considered to be indispensable for the treatment of cancer-related skeletal events, such as bone metastasis. The most common of these drugs are the bisphosphonates, which represent one of the most significant advances over the last 10 years in the field of supportive care and cancer. They are used for the treatment of cancer-induced hypercalcemia, for the prevention and treatment of postmenopausal osteoporosis, for patients with bone metastases secondary to breast cancer and multiple myeloma. A third-generation bisphosphonate, zolendronate, has been shown to minimize the destructive consequences of bone metastases and to exert a profound effect on tumor-induced osteolysis and tumor growth in bone. Zoledronate is already used for the treatment of hypercalcemia of malignancy, multiple myeloma-related osteolytic events and for patients with documented bone metastases from solid tumors in conjunction with standard antineoplastic therapy. The structure-function activity of the three generations of bisphosphonates developed to date, the in vitro models used for studying their effects on osteoclasts and osteoblasts, as well as the results of clinical trials obtained by the third generation bisphosphonate, zoledronic acid, are presented.

Animals↗
PubMed2006

[Nutrition-related bone disease].

Bone disorders clearly related to nutrition are osteomalacia and osteoporosis. Osteomalacia is caused by a deficiency of vitamin D or a disturbance of its metabolism. Dietary deficiency of phosphate or excess of aluminum or cadmium will also cause osteomalacia. Osteoporosis is associated with low intake of calcium and other nutrients. Dietary copper deficiency might stimulate bone metabolism and increase in hip fractures. Excess vitamin A intake was also associated with lower bone mineral density and higher risk of hip fractures. Excess vitamin D sometimes causes mental simplicity, congenital heart disease and calcification of soft tissue. Therefore not only diet but also drugs and supplements of nutrients should be carefully observed in older women.

Aged↗
PubMed1996

Biochemical markers for non-invasive diagnosis of hyperparathyroid bone disease and adynamic bone in patients on haemodialysis.

UNLABELLED: The diagnostic and predictive value of serum intact parathyroid hormone (iPTH) and osteocalcin (bone Gla protein, BGP), alone or in combination, have been examined in only a small number of haemodialysis patients. METHODS: We studied prospectively 114 patients (46 women, 68 men; mean age 52 +/- 12 years) on regular haemodialysis for a mean of 55 (6-185) months. All patients underwent labelled transiliac bone biopsy, and serum levels of iPTH, BGP and alkaline phosphatase were determined. RESULTS: Seventy-one patients (62%) showed histological findings of hyperparathyroid bone disease, 24 (21%) mixed bone disease, six (5.5%) osteomalacia and 13 (11.5%) adynamic bone. Bone aluminium deposition over more than 25% of the trabecular bone interface was found in 66 patients (58%). Serum iPTH and BGP correlated with the majority of histomorphometric indices of bone formation, mineralization and resorption (r > 0.5, P < 0.01). iPTH levels > or = 200 pg/ml and BGP > or = 50 ng/ml were found to be indicative of hyperparathyroid bone disease, whilst iPTH levels < 65 pg/ml and BGP < 20 ng/ml were indicative of adynamic bone. However, the positive predictive value of these indices was limited (less than 80%), although their negative predictive value, especially when used in combination, was good (more than 90%) and the exclusion of hyperparathyroid bone disease and adynamic bone was possible. The diagnostic and predictive value of these bone markers were improved when patients with bone aluminium deposition were excluded. CONCLUSIONS: Diagnosis of hyperparathyroid bone disease and adynamic bone is difficult on the basis of iPTH and BGP, especially when bone aluminium deposition is prevalent. However, using these bone markers, preferably in combination, the exclusion of these lesions is feasible.

Adult↗